1. Field of the Invention
This invention relates to a method of monitoring dialysis patients to ensure that there is adequate dialysis.
2. Description of the Related Art
Dosimetry of dialytic treatment of end-stage renal disease (ESRD) is traditionally specified in terms of time or duration of dialysis. Like the elevation of blood pressure in hypertension or the elevation of sugar in diabetes, ESRD manifests itself with elevation of retention products. Although there is no ideal marker to represent uremic toxins, urea is the best marker, and currently the goal of dialysis is primarily aimed at clearance of urea. Urea level is subject not only to urea removal by dialysis in ESRD, but also to urea generation by protein catabolism and the level of protein intake. A high blood urea nitrogen (BUN) is generally accompanied by increased morbidity. Middle-sized molecules such as vitamin B.sub.12 and larger molecules like parathormone (PTH) and .beta..sub.2 microglobulins have yielded poor correlations with adequate dialysis. Thus, dialysis therapy is geared toward the reduction of urea and other uremic toxins so that their concentrations approach almost normal level.
Use of the index of time or duration of dialysis is the current method used to determine the adequacy of dialysis. This method rather than prescribing a particular dosage of treatment can present problems for patients whose reaction to dialysis does not follow the predicted pattern. Recent studies have pointed to the use of time as an end-point in dialysis therapy as a main factor in the high mortality rates for dialysis in the United States, where the average treatment time is less than 12 hours per week, as compared with Japan and Europe where the average weekly treatment times are 15 and 12 hours per week, respectively. See Brunner et al., Am. J. Kidney Dis. 15:384-396, 1990.
The current methods for calculating dialysis prescription and for assuring the adequacy of dialysis treatment include such indices as KT/V (with K=dialyzer clearance, T=time of dialysis and V=volume of distribution of urea, which may change due to ultrafiltration); the time average concentration of blood urea (TAC.sub.urea), the protein catabolic rate (PCR) and the urea reduction ratio (URR). These have recently been reviewed by Hakim et al., Am. J. Kidney Dis. 20:107-124, 1992. KT/V has been calculated in the past from the equation: KT/V=-In(C.sub.t /C.sub.0 -0.008t-UF/W where C.sub.t is the postdialysis urea level and C.sub.0 is the predialysis urea level; t is the time; UF is the ultrafiltrate removed; and W is the postdialysis weight (Daugirdas, JT, Int. J. Artif. Organs 12:420-427, 1988). TAC.sub.urea represents an average urea concentration, and reflects exposure to the uremic toxin urea, which should generally be below 50 mg/dl for a low morbidity. The indices TAC.sub.urea and PCR, while serving as relevant indicators of adequacy of dialysis, cannot be used to prescribe dialysis. The methods used for defining the dialysis prescription time dose are all based on indices derived from urea kinetic studies, which involve arguably questionable assumptions and estimates, and are indirect techniques.
It is therefore an object of this invention to provide a reliable method for defining the end-point of dialysis to insure the adequacy of dialysis.
It is a further object of this invention to provide a non-invasive, accurate method of determining whether dialysis has to proceed for a sufficient time, utilizing measurements of urea concentration in the effluent dialysate.
Other objects and advantages will be more fully apparent from the following disclosure and appended claims.